Effects of Long-Term Hypoxia and Pro-Survival Cocktail in Bone Marrow-Derived Stromal Cell Survival

Kim, Saejeong; Chaudhry, Aneeka; Lee, Inae; Frank, Joseph A.

doi:10.1089/scd.2013.0297

Cited by 10 publications

(6 citation statements)

References 41 publications

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“…There are several important differences between these investigations. For example, in this study BMSCs were challenged to hypoxia for 72 h in 1% FBS medium, for the BMSCs failed to proliferate in serum-free conditions [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

Zhang

Liu

et al. 2016

Oncotarget

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Bone marrow mesenchymal stem cells (BMSCs) transplantation has shown great promises for treating various brain diseases. However, poor viability of transplanted BMSCs in injured brain has limited the therapeutic efficiency. Hypoxia-ischemic injury is one of major mechanisms underlying the survival of transplanted BMSCs. We investigated the mechanism of preconditioning of BMSCs with hydrogen sulfide (H2S), which has been proposed as a novel therapeutic strategy for hypoxia-ischemic injury. In this study, we demonstrated that preconditioning of NaHS, a H2S donor, effectively suppressed hypoxia-ischemic-induced apoptosis whereby the rise in Bax/Bcl-2 ratio. Further analyses revealed Akt and ERK1/2 pathways were involved in the protective effects of NaHS. In addition, NaHS preconditioning increased secretion of BDNF and VEGF in BMSCs. Consistent with in vitro data, transplantation of NaHS preconditioned BMSCs in vivo further enhanced the therapeutic effects of BMSCs on neuronal injury and neurological recovery, associated with increased vessel density and upregulation of BDNF and VEGF in the ischemic tissue. These findings suggest that H2S could enhance the therapeutic effects of BMSCs. The underlying mechanisms might be due to enhanced capacity of BMSCs and upregulation of protective cytokines in the hypoxia tissue.

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Section: Discussionmentioning

confidence: 99%

Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

Zhang

Liu

et al. 2016

Oncotarget

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“…In addition, before exposing MSC to the severe ischemia at the site of injury (from 0.4% to 2.3% O 2 ), the ex vivo preconditioning of the cells in 1–3% oxygen tension may be a valid strategy for preventing apoptosis of transplanted cells [Rosová et al, ]. By using in vivo experimental models or bone marrow derived cells, other authors demonstrated that the long exposure to low oxygen tension improves the osteogenic and angiogenic potential of MSC [Rosová et al, ; Volkmer et al, ; Sheehy et al, ; Kim et al, ].…”

Section: Discussionmentioning

confidence: 99%

Prolonged Exposure to Hypoxic Milieu Improves the Osteogenic Potential of Adipose Derived Stem Cells

Fotia

Massa

Boriani

et al. 2015

J of Cellular Biochemistry

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Mesenchymal stem cells (MSC) have been widely used in orthopedics for several applications. Conventionally, MSC are maintained under 21% O2 which does not reflect the real O2 tension in vivo. Recently, it was reported that different O2 conditions can give different cellular responses. Here, we investigated whether prolonged exposure to hypoxia affects the osteogenic differentiation of adipose-derived stem cells (ASC). ASC from six individuals were cultured under "low" (2-3%) or "air" (21%) oxygen tensions, either without or with osteogenic stimuli. The effect of the O2 tension was evaluated on cell proliferation, surface antigens, stemness and bone-related genes expression, alkaline phosphatase activity (ALP), mineralization activity, and release of osteogenic growth factors. Without differentiating stimuli, hypoxia favored ASC proliferation, reduced the number of CD184+ and CD34+ cells, and preserved the expression of NANOG and SOX2. The combination of hypoxia and osteogenic medium induced a high proliferation rate, a rapid and more pronounced mineralization activity, a higher expression of genes related to the MSC differentiation, a higher release of mitogenic growth factors (bFGF, PDGF-BB), and the decrease in TGF-β secretion, an inhibitor of the early stage of the osteoblast differentiation. We demonstrated that hypoxia acts dually, favoring ASC proliferation and the maintenance of the stemness in the absence of osteogenic stimuli, but inducing the differentiation in a bone-like microenvironment. In conclusion, prolonged cell culture in hypoxic microenvironment represents a proper method to modulate the stem cell function that may be used in several applications, for example, studies on bone pathophysiology or bone-tissue engineering.

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“…Human MSCs from 23 year old female (provided by NIH Center for Bone Marrow Stromal Cell Transplantation under an approved Intramural Research Branch protocol http://sigs.nih.gov/bmsctc) were culture‐expanded in α‐minimum essential medium (Life Technologies, Carlsbad, CA, http://www.lifetech.com) with 20% lot‐selected fetal bovine serum (Gemeni Bio‐products, Sacramento, CA) at 37°C under 5% CO 2 and 95% air. Early passage cells (3–5) were used for studies.…”

Section: Methodsmentioning

confidence: 99%

Cyclooxygenase-2 or Tumor Necrosis Factor-α Inhibitors Attenuate the Mechanotransductive Effects of Pulsed Focused Ultrasound to Suppress Mesenchymal Stromal Cell Homing to Healthy and Dystrophic Muscle

et al. 2015

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Maximal homing of infused stem cells to diseased tissue is critical for regenerative medicine. Pulsed focused ultrasound (pFUS) is a clinically relevant platform to direct stem cell migration. Through mechanotransduction, pFUS establishes local gradients of cytokines, chemokines, trophic factors (CCTF) and cell adhesion molecules (CAM) in treated skeletal muscle that subsequently infused mesenchymal stromal cells (MSC) can capitalize to migrate into the parenchyma. Characterizing molecular responses to mechanical pFUS effects revealed tumor necrosis factor-alpha (TNFα) drives cyclooxygenase-2 (COX2) signaling to locally increase CCTF/CAM that are necessary for MSC homing. pFUS failed to increase chemoattractants and induce MSC homing to treated muscle in mice pretreated with ibuprofen (non-specific COX inhibitor) or etanercept (TNFα inhibitor). pFUS-induced MSC homing was also suppressed in COX2-knockout mice, demonstrating ibuprofen blocked the mechanically-induced CCTF/CAM by acting on COX2. Anti-inflammatory drugs, including ibuprofen, are administered to muscular dystrophy (MD) patients and ibuprofen also suppressed pFUS-induced homing to muscle in a mouse model of MD. Drug interactions with cell therapies remain unexplored and are not controlled for during clinical cell therapy trials. This study highlights potentially negative drug-host interactions that suppress stem cell homing and could undermine cell-based approaches for regenerative medicine.

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Effects of Long-Term Hypoxia and Pro-Survival Cocktail in Bone Marrow-Derived Stromal Cell Survival

Cited by 10 publications

References 41 publications

Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

Prolonged Exposure to Hypoxic Milieu Improves the Osteogenic Potential of Adipose Derived Stem Cells

Cyclooxygenase-2 or Tumor Necrosis Factor-α Inhibitors Attenuate the Mechanotransductive Effects of Pulsed Focused Ultrasound to Suppress Mesenchymal Stromal Cell Homing to Healthy and Dystrophic Muscle

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